Method and apparatus for performing peritoneal ultrafiltration

ABSTRACT

Method and apparatus for ultrafiltration of a patient being overhydrated due to congestive heart failure, comprising a cassette having four inlets/outlets. A patient tube is connected to a patient connector, intended to be connected to a patient line for access to a peritoneal cavity of the patient. The patient tube comprises a flow pump for addition and removal of a peritoneal fluid between the cassette and the peritoneal cavity. The fluid is introduced into an intermittent bag controlled by an intermittent valve and then returned the same way back to the peritoneal cavity. Glucose is metered into the fluid entering the peritoneal cavity by means of a glucose pump. Glucose is replenished continuously or intermittently for keeping a concentration of the osmotic agent substantially constant in the peritoneal cavity. After treatment, the peritoneal fluid is drained to a drain bag, wherein the drain tube comprises a drain valve and an albumin filter.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Divisional of co-pending application Ser. No.15/122,103, filed on Aug. 26, 2016, which is the National Phase under 35U.S.C. § 371 of International Application No. PCT/SE2015/000011, filedon Feb. 27, 2015, which claims the benefit under 35 U.S.C. § 119(a) toPatent Application No. 1430027-1, filed in Sweden on Feb. 28, 2014, allof which are hereby expressly incorporated by reference into the presentapplication.

FIELD OF INVENTION

The present invention relates to an apparatus and method for performingperitoneal ultrafiltration of a patient, for example due to congestiveheart failure.

BACKGROUND

Diuretic-resistant congestive heart failure is a problem of growingsignificance. It is related closely to the cardio-renal syndrome, whichis characterized by chronic abnormalities in cardiac function, causingimpaired renal function and progressive chronic kidney disease.

Congestive Heart Failure patients can benefit from fluid removal byultrafiltration. These patients normally have functional kidneys, butsuffer from fluid overload. The kidneys of these patients are generallyhealthy but are not fully functioning due to the failing heart withincreased venous blood pressure and sometimes low arterial bloodpressure. Because the kidneys are not fully functioning, fluids build upin the patient and the fluid overload contributes to stress on thealready failing heart. In addition, secretion of certain electrolytes,such as sodium ions and potassium ions, may be impaired.

The proper control of sodium and water balance is of vital importancebecause up to 80% of hospitalizations from Congestive Heart Failure aredue to acute overhydration and only 5% are due to low cardiac output.

The patent document U.S. Pat. No. 7,135,008 B2 discloses a method andapparatus for the extracorporeal treatment of blood by utilizing aperipherally inserted dual lumen catheter assembly for the continuousremoval and return of blood for renal replacement treatment, inparticularly, treatment of congestive heart failure and fluid overloadby ultrafiltration. A catheter is inserted in a peripheral vein andmaneuvered upward through the vascular system to access the reservoir ofblood in the large or great veins for continuous blood withdrawal andtreatment. Air-tight connectors are incorporated in the catheterassembly to overcome the untoward effects of negative pressure in bloodwithdrawal.

However, ultrafiltration via extracorporeal treatment of blood, resultsin risks associated with access to the vascular system. In addition, theultrafiltration may be excessive resulting in hypotension.

A promising ultrafiltration method which do not use extracorporeal bloodtreatment is peritoneal dialysis, in which the endogenous peritonealmembrane is used for ultrafiltration. A peritoneal ultrafiltration fluidis installed in the peritoneal cavity. The fluid comprises an osmoticagent, such as glucose or Icodextrin or others, causing ultrafiltration.Peritoneal ultrafiltration is more gentle to the patient and seldomresults in hypotension. In addition, the peritoneal ultrafiltration maybe used daily outside the hospital without the need for medicallytrained professionals.

With the present PD regiments, glucose based fluids must be replacedevery four hours and has optimal ultrafiltration for only 2 to 3 hours.Each replacement takes about one hour and increases the risk ofinfection. This reduces the freedom and quality of life for thepatients. Automated PD dialysis machines are know in the prior art, butthey are cumbersome and are not optimized for merely ultrafiltration,but concentrate on urea nitrogen removal.

However, the use of glucose may result in the absorption of glucose intothe circulation, which may lead to hyperglycemia, hyperinsulinemia, andobesity. Icodextrin may cause other problems.

It is also known that peritoneal dialysis often results in removal ofalbumin and other important constituents of the blood and body.

Thus, there is a need for a peritoneal dialysis fluid comprisingglucose, which is optimized with regard to peritoneal ultrafiltration ofpatients with heart failure. In addition, there is a need for a methodand an apparatus for performing peritoneal ultrafiltration.

SUMMARY OF THE INVENTION

Accordingly, an object of the present invention is to mitigate,alleviate or eliminate one or more of the above-identified deficienciesand disadvantages singly or in any combination.

In an aspect, there is provided an apparatus for ultrafiltration of apatient, for example a patient being overhydrated due to congestiveheart failure, comprising: a cassette having four inlets/outlets; apatient tube for connection of a patient connector, intended to beconnected to a patient line for access to a peritoneal cavity of thepatient, to a first inlet of the cassette, wherein the patient tubecomprises a flow pump for addition and removal of a peritoneal fluidbetween the cassette and the peritoneal cavity; an intermittent tube forconnection of an intermittent bag to a second inlet of the cassette,wherein the intermittent tube comprises an intermittent valve; a draintube for connection of a drain bag to a third inlet of the cassette,wherein the drain tube comprises a drain valve; and a glucose tube forconnection of a glucose bag comprising glucose at a high concentrationto a fourth inlet of the cassette, wherein the glucose tube comprises anglucose pump for addition of glucose to the cassette; whereby glucose isreplenished for keeping a concentration of the osmotic agentsubstantially constant in the peritoneal cavity.

According to an embodiment, the first and second inlets of the cassetteare arranged at one side of the cassette and the third and fourth inletsof the cassette are arranged at the other side of the cassette. Theintermittent bag may be smaller than 500 ml, 400 ml, 300 200 ml, such as160 ml. A glucose meter may be arranged for measuring glucoseconcentration of peritoneal fluid entering or leaving the cassette. Theglucose meter may be arranged in said drain tube downstream of saiddrain valve, whereby glucose concentration is measured only when thedrain valve is open. A pressure meter may be arranged for measuringpressure of peritoneal fluid adjacent the patient connector. Anotherpressure meter may be arranged for measuring pressure inside saidcassette. Moreover, a flow meter may be arranged in the patient tube.

In another embodiment, the intermittent bag is replace by a secondpatient connector, intended to be connected to a second patient line foraccess to the peritoneal cavity of the patient.

In a further embodiment, the patient tube, the patient connector, thepatient line, the first inlet, the cassette, the intermittent tube, theintermittent bag, the second inlet of the cassette, are all arrangedwithout any adsorbent material or dialyzer. The drain tube may comprisean albumin filter for preventing albumin from passing to the drain bagduring draining of the peritoneal cavity.

In another aspect, there is provided a method for ultrafiltration of apatient, for example a patient being overhydrated due to congestiveheart failure, which patient has a predetermined volume of peritonealfluid installed in a peritoneal cavity; comprising: removing peritonealfluid from the peritoneal cavity, via a patient line, a patientconnector, and a flow pump to a first inlet of a cassette, and further,via a second inlet, an open intermittent valve, and an intermittent tubeto an intermittent bag; subsequent return of peritoneal fluid from saidintermittent bag the same way in the opposite direction; whereinconcentrated glucose solution is, during said return of peritonealfluid, simultaneously entered to the cassette via a fourth inlet bymeans of a glucose pump from a glucose concentration fluid bag for beingdiluted in the flow of peritoneal fluid and entered into the peritonealcavity; whereby glucose is replenished to the peritoneal fluid in theperitoneal cavity.

In an embodiment, the removal flow and return flow may pass throughtubes and spaces free from adsorbent materials and/or free fromdialyzers.

In another embodiment, the peritoneal cavity is drained from peritonealfluid after finalized peritoneal ultrafiltration, by removing peritonealfluid from the peritoneal cavity to a drain bag by means of said flowpump, through an albumin filter, until the peritoneal cavity is empty,whereupon the flow pump is reversed and returns a small amount ofperitoneal fluid from the drain bag via the albumin filter to theperitoneal cavity in order to return albumin gathered by the albuminfilter. The draining of the peritoneal fluid may take place via thepatient line, the patient connector, and the flow pump to the firstinlet of the cassette, and further, via a third inlet, an open drainvalve and the albumin filter to the drain bag.

In a further embodiment, the removal flow and the return flow each timemay comprise a maximum volume of less than 500 ml, 400 ml, 300 ml, 200ml, such as 160 ml.

In a still further embodiment, a peritoneal fluid comprising less than0.5%, such as less than 0.2%, for example 0.1% or 0% glucose isinitially introduces into the peritoneal cavity before the start of theremoving and returning of the peritoneal fluid, whereupon the glucoseconcentration is increased to a predetermined treatment concentrationduring a predetermined time, such as during between 30 minutes and 60minutes.

In a further aspect, there is provided a method for ultrafiltration of apatient, for example a patient being overhydrated due to congestiveheart failure, which patient has a predetermined volume of peritonealfluid installed in a peritoneal cavity, comprising: removing peritonealfluid from the peritoneal cavity, via a first patient line, a patientconnector, and a flow pump to a first inlet of a cassette, and further,via a second inlet/outlet of the cassette, an open intermittent valve,and an intermittent tube to a second patient line; wherein concentratedglucose solution is, during said flow of peritoneal fluid,simultaneously metered to the cassette via a fourth inlet by means of aglucose pump from a glucose concentration fluid bag for being diluted inthe flow of peritoneal fluid and entered into the peritoneal cavity;whereby glucose is replenished to the peritoneal fluid in the peritonealcavity.

In a still further aspect, there is provided a use of a peritoneal fluidfor treatment of overhydration due to congestive heart failure byperitoneal ultrafiltration, wherein peritoneal fluid is removed from theperitoneal cavity of the patient and returned to the peritoneal cavityreplenished with glucose, for maintaining a substantially constantconcentration of glucose in the peritoneal fluid.

BRIEF DESCRIPTION OF THE DRAWINGS

Further objects, features and advantages of the invention will becomeapparent from the following detailed description of embodiments of theinvention with reference to the drawings, in which:

FIG. 1 is a schematic diagram of a first embodiment of an apparatus forproviding an ultrafiltration fluid to a patient.

FIG. 2 is a schematic diagram of a second embodiment of the apparatusfor providing an ultrafiltration fluid to a patient.

FIG. 3 is a schematic diagram of a third embodiment of the apparatus forproviding an ultrafiltration fluid to a patient.

DETAILED DESCRIPTION OF EMBODIMENTS

Below, several embodiments of the invention will be described. Theseembodiments are described in illustrating purpose in order to enable askilled person to carry out the invention and to disclose the best mode.However, such embodiments do not limit the scope of the invention.Moreover, certain combinations of features are shown and discussed.However, other combinations of the different features are possiblewithin the scope of the invention.

FIG. 1 discloses a patient 1, which is provided with a patient line 3,which may be a conventional peritoneal catheter. The patient line 3connects the patient's peritoneal cavity 2 with the surroundingenvironment. The patient line 3 ends with a connector 4 of standardtype, for example a Luer connector. The provision of the patient line isa standard procedure and is made at a hospital. After a few days, thepatient line may be used for entering and removing a peritoneal fluidinto the peritoneal cavity. The peritoneal fluid contacts a peritonealmembrane comprising capillary blood vessels. The peritoneal fluid willexchange ions and substances with the blood. Peritoneal dialysis hasbeen performed routinely for several decades and was used already duringthe 1940's.

An apparatus 10 according to a first embodiment of the invention isshown in FIG. 1 and comprises a tube set 20, having a cassette 25comprising four inlets from: a flow pump 15, a glucose pump 16, a drainvalve 17 and an intermittent valve 18.

The pumps 15 and 16 are shown as peristaltic pumps of a type commonlyused in a dialysis apparatus. However, other types of pumps may be used.

The valves are electrically operated pinch valves which act upon a tubefor occlusion of the tube. However, any type of valve may be used,including manually operated clamps.

The tube set comprises a connector 21, which mates with the connector 4of the patient line 3. The connector 21 is arranged at a distal end of apatient tube 22. The patient tube 22 comprises a port 23 adjacent theend connector 21.

A proximal end of the patient tube 22 is connected to a pump segment 24passing through the flow pump 15. The other end of the pump segment 24is connected to a first inlet 25 a of the cassette 25. Thus, thecassette 25 is connected to the end connector 21.

The tube set further comprises a glucose bag 26, which is connected tothe cassette 25 via a glucose tube 27. The glucose tube 27 is connectedto a pump segment 29 passing through the glucose pump 16 and further toa fourth inlet 25 d of the cassette 25. A connector or spike 28 isarranged at the end of the glucose tube 27 for being inserted in theglucose bag 26 for establishing fluid communication between the glucosebag 26 and the glucose tube 27. Thus, the glucose bag 26 is connected tothe cassette 25. Alternatively, the glucose bag is permanently attachedto the glucose tube 27 or connected to the glucose tube by a Luerconnector or other similar connector.

The tube set further comprises a drain bag 30, which is connected to adrain tube 31 via a connector 32. The drain tube 31 is connected to athird inlet 25 c of the cassette 25. The drain valve 17 acts upon thedrain tube 31 for occluding the drain tube when activated. Thus, thedrain bag 30 is connected to the cassette 25.

The tube set further comprises an intermittent bag 33 connected to anintermittent tube 34. The intermittent tube 34 is connected to a secondinlet 25 b of the cassette 25. The intermittent pinch valve 18 acts uponthe intermittent tube 34 for occluding the intermittent tube whenactivated. Thus, the intermittent bag 33 is connected to the cassette25.

The tube set may be PVC tubes of a medical grade. The pump segments maybe made by silicon tubes. The peristaltic pump may also operate as aflow meter, since a specific volume of fluid is normally pumped perrevolution of the pump.

It is noted that first 25 a and second 25 b inlets of the cassette 25are arranged at the on (left) side of the cassette 25. These inlets areassociated with the handling of the peritoneal fluid which is passedbetween the peritoneal cavity and the intermittent bag 33.

On the other hand, the third 25 c and fourth 25 d inlets are arranged atthe other (right) side of the cassette 25. These inlets are arranged forbeing connected to external bags, namely the glucose bag 26 and thedrain bag 30. This arrangement results in a more safe operation of thedevice in that the different connections will not easily be mixed up.Since the patient tube 22 extends to the left and the other tubes 27, 31to the right, it is easy to make the right connection of the patienttube 22 to the patient line 3 and not intermix it with the otherconnectors 28 and 32.

The apparatus 10 and tube set 20 may be arranged in four enclosures asindicated by broken lines in FIG. 1. Thus, the two pumps 15, 16 and thetwo pinch valves 17, 18 may be arranged in one enclosure as indicated bybroken lines 11, which additionally may comprise necessary electroniccircuits for operating the apparatus, including any batteries, processorboard and graphical interface including operating buttons. Theintermittent bag 30 may be arranged in a separate enclosure 12 and theglucose bag 26 may be arranged in a separate enclosure 13 and the drainbag may be arranged in a separate enclosure 14. All the enclosures 11,12, 13, 14 may be arranged in a wearing equipment intended to be worn bythe patient.

Alternatively, the apparatus 10 is assembled inside a bag or supportingstructure, and the tube set 20 is arranged at the apparatus duringinitiation thereof.

The apparatus 10 according to the first embodiment may be operated inthe following manner.

The apparatus 10 is set-up by arranging the wearing equipment on apatient. First, the tube set should be primed by passing a sterile fluidalong the fluid lines. Such priming ensures that possible toxic productsat the inner side of the tubes are removed. In addition, any bacteriamay be removed, for example originating from an aseptic handling of thetube set. Moreover, any air inside the tube set is removed. Finally, apossible leak of the tube set will be discovered, so that another setcan be used.

One example of a priming sequence is the following: A priming bag 35shown by broken lines in FIG. 1 and comprising sterile isotonic primingsolution (for example about 2 liters of sterile 0.9% saline solution) isconnected to the port 23 at the distal end of the patient tube 22. Theend connector 21 is closed by a lid (not shown). When a priming buttonis pressed, the priming procedure starts.

The priming procedure starts with opening of the drain valve 17,whereupon the flow pump 15 is started and operated in a forward(clockwise) direction. Fluid from the priming bag passes via port 23 topatient tube 22 and further to the pump segment 24 and to the cassette25. From the cassette 25, the only open connection is via drain valve 17to the drain bag 30.

After some time, the drain valve 17 is closed and the intermittent valve18 is opened, whereupon the priming fluid is pumped into theintermittent bag 33, until it is (almost) full. Then, the flow pump 15is operated in its reverse (counterclockwise) direction for removing thepriming fluid from the intermittent bag and back to the priming bag,until the intermittent bag is empty. Possible air inside theintermittent bag is removed in this step. Then, the intermittent valve18 is closed and the drain valve 17 is opened and the flow pump 15 isagain operated in the forward direction, for pumping the rest of thepriming fluid to the drain bag 30. During or before priming of thepatient tube 22, a glucose bag 26 is connected to the spike 28,whereupon the glucose pump 16 is started. A small amount of glucosesolution is pumped from the glucose bag 26 via the glucose tube 27 tothe cassette 25 for rinsing the glucose tube.

When the priming is completed and the priming bag 35 is empty, it may beremoved from the port 23, which is closed. Before the priming bag isempty, the lid at the end of connector 21 may be removed for a shorttime duration, whereby sterile fluid rinse the connector 21, whereuponthe lid is added again.

The drain bag 30, which is filled with priming fluid, is removed and anew bag comprising peritoneal fluid to be used for peritonealultrafiltration is connected to connector 32. The patient is connectedto the patient tube 22 by removing the lid from the patient connector 21and attaching the connector to the patient line connector 4. The drainvalve 17 is opened and the flow pump 15 is operated in its reversedirection for entering the peritoneal fluid from bag 30 into theperitoneal cavity of the patient.

When the treatment is ended (after several hours), surplus fluid isfinally removed from the patient to the drain bag.

Other priming procedures may be used. For example, the priming fluidcollected in drain bag 30 may be pumped back to the priming bag 35 in alast step, whereupon the priming bag 35 is discarded with its contents.

Another method may be to pump the priming fluid from priming bag 35 tothe intermittent bag (a priming fluid volume of 200 ml would besufficient) by opening the intermittent valve 18 and operating the pump15 in the forward direction, until the intermittent bag is filled. Then,the pump 15 is reversed and the fluid from the intermittent bag 33 isreturned together with a small amount of fluid from the glucose bag 26until the intermittent bag 33 is empty, whereby possible air in theintermittent bag and cassette is removed. Finally, a small amount of aperitoneal fluid in the drain bag 30 is pumped to the priming bag byopening drain valve 17 and closing intermittent valve 18. Now all lineshave been primed as desired and the priming bag 35 can be removed andperitoneal fluid in the drain bag 30 can be installed in the patient.

Alternatively, a conventional CAPD-bag-set may be connected to the port23 or connector 4 for the initial installation of initial peritonealfluid and peritoneal fluid may be entered into the peritoneal cavity bygravity feed. In this case, the drain bag 30 is initially empty. In thesame way, the final emptying of the peritoneal cavity after a fulltreatment may take place by connection of a separate drain bag to theport 23 and draining the peritoneal cavity by gravity by placing thedrain bag in a low position.

If the peritoneal fluid in bag 30 comprises glucose of a desiredconcentration (such as 1.5%), the glucose pump 16 is not activatedduring the initial introduction of peritoneal fluid to the peritonealcavity. However, in another embodiment, the peritoneal fluid in bag 30comprises all components of a peritoneal solution except glucose, andglucose is added during the initial installation in a desired proportionby activating the glucose pump 16. Alternatively, the glucoseconcentration of the peritoneal fluid is slowly increased during thefirst cycles, for example during 30 to 60 minutes, to a predeterminedglucose concentration. The initial glucose concentration of theinitially installed peritoneal fluid may be less than 0.5%. The glucoseconcentration may be 0.1%, corresponding to normal physiological glucoseconcentration, or 0% as indicated above.

The standard components of a peritoneal solution in addition to glucoseare: sodium chloride, sodium lactate, calcium chloride and magnesiumchloride. In addition, potassium chloride may be included. Lactate maybe replaced by acetate or bicarbonate.

When the peritoneal fluid comprising glucose has been installed in theperitoneal cavity, exchange of substances takes place between theinstalled fluid and the blood. In particular, glucose is slowly absorbedby the blood, since the concentration of glucose in the peritoneal fluidis larger than the glucose concentration in blood. However, since theabsorption of glucose is slow, water will diffuse in the other directionthrough the walls of the capillaries into the peritoneal cavity, due toosmotic pressure of the glucose solution, in order to dilute theperitoneal fluid. As long as the concentration of glucose in theperitoneal fluid is larger than in blood, such water transport takesplace. Such water transport is equivalent to ultrafiltration. Since theblood will lose some water, this water loss will be replaced in theblood from other portions of the body, resulting in removal of surpluswater from the tissue. However, a too fast removal of water from theblood should be avoided, since the blood may become too concentrated andviscous.

The glucose, which has been absorbed into the blood, is taken care of bythe body system, in particular the insulin system, which keeps theglucose concentration in blood within safe limits, normally between 4 to7 mmol/liter, corresponding to 0.72 to 1.26 g/l.

The glucose absorbed by the blood from the peritoneal cavity needs to bereplaced in the peritoneal cavity in order to maintain the glucosegradient and ultrafiltration. The principle used in the embodiments isthat a more or less continuous replacement of glucose is performed inorder to achieve a substantially constant ultrafiltration, which isbelieved to alleviate symptoms.

This is accomplished in the following manner. After a short time of forexample twenty minutes, the intermittent valve 18 is opened and the flowpump 15 is operated in the forward direction, whereby fluid is removedand pumped from the peritoneal cavity via the cassette 25 to theintermittent bag, which may have a volume of about 160 ml. The flow ratemay be about 16 ml/min. When a predetermined amount of fluid has beenentered into the intermittent hag, for example 100 ml (or a maximum of160 ml), the flow pump 15 is operated in the reverse direction forreturning the fluid in the intermittent bag 33 to the patient. Theglucose pump 16 continuously adds glucose to the returned peritonealfluid in the cassette 25. The addition of glucose takes place at a ratecalculated to replaces the glucose, which has been absorbed by theblood. The procedure is repeated intermittently after another twentyminutes etc.

Thus, the peritoneal fluid in the peritoneal cavity is replenished withfresh glucose intermittently. However, the replenishment cycle takesplace relatively often, so that the glucose concentration in theperitoneal fluid inside the peritoneal cavity is substantially constant.Thus, a substantially constant ultrafiltration takes place.

The intermittent bag 33 is designed to be smaller than the amount offluid installed in the peritoneal cavity. This makes it impossible toremove all peritoneal fluid in the peritoneal cavity. The intermittentbag 33 should be smaller than 500 ml, such as smaller than 400 ml, 300ml or even smaller than 200 ml. In the present embodiment, theintermittent bag is 160 ml. If all peritoneal fluid inside theperitoneal cavity is removed, the ultrafiltration stops. Since the timefor removal and installation of peritoneal fluid is relatively long andshould be gentle, such ultrafiltration stops would be undesirable. Thus,only a small portion of the peritoneal fluid in the peritoneal cavity isremoved during each step or cycle. The amount removed need not be thecomplete volume of the intermittent bag, but may be smaller, such as 100ml in a bag of 160 ml as mentioned above.

The flow pump may be operated at a speed of 20 ml/min. Thus, the removalof 100 ml of fluid from the peritoneal cavity and return of the sameamount (replenished by glucose) may take about 10 minutes. Then, theflow pump may be kept stopped for 0 to 50 minutes, until a nextreplacement cycle is started. Thus, the total replacement cycle is 10 to60 minutes.

Ultrafiltration also results in that the volume of peritoneal fluidinside the peritoneal cavity increases. Such increase of volume mayresult in that the pressure inside the peritoneal cavity increases,which counteracts ultrafiltration.

In order to counteract such increase of volume inside the peritonealcavity, the following procedure may be used. At the start of areplenishment cycle, the intermittent valve 18 is kept closed and thedrain valve 17 is opened and a predetermined amount of peritoneal fluidis removed and pumped into the drain bag 30, for example 50 ml perintermittent cycle of 30 minutes. Then, the drain valve 17 is closed andthe intermittent valve 18 is opened and the procedure continues asdescribed above. Thus, a small amount of fluid is removed for everycycle.

Alternatively, such fluid removal may be performed only each fifth cycleor at any time desired.

The fluid removal does not need to be synchronized with thereplenishment. If the patient feels or suspect or measures that thepressure inside the peritoneal cavity increases, for example so that thepatient feels discomfort, the patient may operate a drain button, whichdrains a predetermined amount of fluid by opening the drain valve 17 andoperating the flow pump 15 in the forward direction until apredetermined amount has been removed, for example 100 ml.

In another alternative embodiment, there is a pressure sensor, whichactivates a drain cycle if the pressure inside the peritoneal cavityincreases above a predetermine threshold, see further below. The draincan also take place at predetermined time intervals, for example eachhour.

It is noted that the amount of peritoneal fluid inside the peritonealcavity should be optimal, so that the entire peritoneal membrane is usedfor exchange of ultrafiltration water, which promotes ultrafiltration,but so that as small as possible overpressure exists inside theperitoneal cavity, which counteracts ultrafiltration. If the installedvolume is too small, only a portion of the peritoneal membrane is used,requiring higher glucose concentrations for achieving a desiredultrafiltration goal. If the pressure is too high, water is pressed backinto the tissue and blood vessels.

The dosage of glucose may be determined in advance and adjustedaccording to a prescription by a doctor. The patient may also adjust thereplenishment of glucose, at least within sonic limits. For example, ifthe patient feels pain, this may be due to a too high glucoseconcentration, and the patient may decrease such concentration bypressing a button. Pressing the button may result in reduction ofglucose replenishment during the next few cycles. Other situations whena decreased replenishment of glucose should be contemplated may be ifthe patient feels dizziness or the blood pressure decreases.

According to an embodiment, glucose is added by a prescribed amount perhour, for example 5 gram glucose per hour. If the glucose concentrationin bag 26 is 20% (200 gram per liter) and if a cycle is performed threetimes per hour, then 8.3 ml glucose fluid should be added each cycle to100 ml peritoneal fluid exchanged each cycle. The concentration in theperitoneal fluid inside the peritoneal cavity will reach a concentrationvalue, at which the consumption will be 5 gram glucose per hour. Thiswill correspond to a desired ultrafiltration for one treatment period,which may be 10 hours during the day, or 6 to 8 hours during the night.The ultrafiltration is measured, and the prescription of the amount ofglucose per hour is adjusted accordingly. The amount of glucose absorbedby a person is highly individual and may also change over time for aspecific patient.

The embodiment described above is used when the patient has a singlelumen patient line. However, the glucose concentration will varyslightly within the intermittent period, up and down around a meanvalue.

The intermittent period should be small compared to the variation ofglucose in the peritoneal cavity. If no replenishment takes place,glucose is absorbed during a period of approximately one to three hours.Thus, the intermittent period for replenishment should be no longer thanone hour. A suitable replenishment cycle or period may be 60, 50, 40, 30or 20 minutes. The replenishment period is calculated as the timebetween the start of each replenishment cycle.

In another embodiment shown in FIG. 2, two patient line or catheters 53a and 53 b are installed in the peritoneal cavity as shown. The twocatheters may be arranged as a dual lumen catheter as is well-known.

In the second embodiment, the second catheter 53 b is connected insteadof or replacing the intermittent bag 33 in the embodiment of FIG. 1.

In the second embodiment, the flow pump 65 may continuously circulateperitoneal fluid into the peritoneal cavity via the second catheter 53 band out from the peritoneal cavity via the first catheter 53 a, byoperating the flow pump 65 in the forward (clockwise) direction and byopening the intermittent valve 68. The glucose pump 66 is also operatedcontinuously for continuous replenishment of glucose. In this manner, aconstant glucose concentration may be obtained in the peritoneal fluidintroduced into the peritoneal cavity.

Alternatively, the glucose pump may be operated intermittently, withshort intervals, for example one action per minute, or with longerintervals, such as each fourth minute.

The tube set according to the second embodiment comprises a patient lineconnector 85 instead of the intermittent bag 33 of the embodiment ofFIG. 1. In addition, a sample port 86 is arranged adjacent the connector85 in the intermittent tube 84.

In other respects, the operation is substantially the same as in thefirst embodiment described in connection with FIG. 1.

The concentrated glucose delivered by the glucose bag is mixed with theperitoneal fluid inside the cassette 75, wherein a thorough mixing willtake place. Because the cassette has a predetermined inner volume of forexample 5 ml, a sufficient time for mixing will prevail.

The patient having heart failure may also have low blood pressure, whichmay compromise the operation of the kidney. The kidney may requiresupport in removal of excess water, since the urine production issmaller than normal. However, the excretion of metabolic waste products,such as urea and creatinine, may normally be sufficient.

However, because of the low urine volume, an insufficient removal ofsodium may prevail. Thus, the peritoneal fluid used in these embodimentsmay be modified by reducing the sodium concentration in the initiallyinstalled peritoneal fluid to for example to 90 mmol/l, which results inremoval of sodium, in addition to removal of water as described above.If the removal of potassium of the kidney is too low, a lowering of thepotassium concentration to 1 mmol/l in the starting fluid may beappropriate, or even no potassium in the installed peritoneal fluid.However, the body is sensitive to low potassium concentration in blood,and a lowering of the potassium concentration (or zero) should becarefully supervised by a doctor.

The patient having heart failure may have a compromised blood pressureas indicated above. Such blood pressure may result in partial withdrawalof capillaries in the peritoneal membrane and adjacent tissue, resultingin less exchange of substances between the fluid in the peritonealcavity and the blood. The result is less ultrafiltration. However, thecontinuous supply of glucose is expected to reduce any tendency for thecapillaries to withdraw, since the body is not exposed to transientconditions. Thus, the continuous, or almost continuous but intermittent,replenishment of glucose is expected to be of great importance forsensitive patients.

The peritoneal membrane is sensitive to excessive exposure to glucose,which may result in peritoneal pain and peritonitis and othercomplications. A gentle exposure of the peritoneal membrane to glucosemay counteract such problems. Accordingly, the initial installation ofPD-fluid into the peritoneal cavity may take place with a lowconcentration of glucose, or even zero glucose. Then, the concentrationof glucose is increased slowly during a predetermined time, such as 30to 60 minutes, to the desired concentration.

Due to the fact that a replenishment of glucose is made continuously orintermittently with short intervals, a low concentration of glucose maybe used and still a desired ultrafiltration may be achieved. This isadvantageous for avoiding pain and peritonitis as well for maintainingthe ultrafiltration function of the peritoneal membrane.

The replenishment of glucose may be controlled or monitored by measuringthe glucose concentration in the effluent fluid from the peritonealcavity. Suppose that the initial concentration of glucose is 1.5% andthe measured concentration in the effluent fluid after 30 minutes hasbeen reduced to 1.3%. In this case, a replenishment of glucose so thatthe inflowing fluid has a concentration of 1.7% may be appropriate. Ifthe effluent fluid glucose concentration still decreases, thereplenishment is increased further, to 1.8%, etc. On the other hand, ifthe effluent concentration is approaching the desired 1.5%, thereplenishment is decreased.

If the patient during the treatment is exposed to hypotension or otherproblems, resulting in withdrawal of capillaries in the peritonealmembrane, this is manifested as a lowering of the ultrafiltration and alowering of glucose absorption. The lowered glucose absorption may bemonitored by a glucose sensor or meter and may result in an alarm to thepatient and/or supervising persons. Then, the treatment may beinterrupted or other actions undertaken for removing the cause ofdecreased absorption and low ultrafiltration.

On the other hand, excessive absorption of glucose to the blood may beencountered during certain conditions, resulting in low glucoseconcentration.

A glucose meter may be arranged in the sample ports 73, 86, 23.Alternatively, a glucose meter may be arranged in the tube set, forexample adjacent the cassette 25, 75.

Since a glucose meter may be sensitive to constant exposure to glucose,the glucose meter 88 may be arranged in the drain tube 31, 81 after thedrain valve 17, 67 as shown in FIG. 3. When the glucose concentrationshould be measured, the drain valve 67 is opened and the pump 65 isoperated in a forward direction for a short time period and themeasurement is performed. In this way, the glucose meter 88 is exposedfor glucose only during short intervals.

A pressure sensor or meter 91 may be arranged in the ports 23, 73, 86 orany other position in the tube system in order to monitor or measure thepressure at or adjacent the connections to the patient line 3, 53 a, 53b. A high pressure during standstill of the flow pump 65 may beindicative of too high a volume inside the peritoneal cavity. Thus,removal of some fluid to drain may be proper as indicated above.

The pressure meter 91 may be a tube of a suitable length connected tothe port 73 as indicated in FIG. 3. Fluid will rise inside the tube andthe height of the water pillar indicates the pressure, for example in cmwaterpillar. Other arrangements may be used, such as a similar pressuremeter in port 86 and/or port 23. In some embodiments, a pressure meterindicating a pressure below atmospheric pressure may be useful, sincenormally the pressures are always above or equal to atmosphericpressures. If a pressure below atmospheric pressure during a long timeis measured, an alarm may be triggered.

A high pressure in port 23 during filling may depend on a partialocclusion of the patient line 3. A partial occlusion of the patient linewould also result in a low pressure during emptying of the cavity. Thus,an alarm may be triggered.

If there is an occlusion or kink of the tube to the patient, i.e. theintermittent tube 84 in the second embodiment, this will be manifestedas a high pressure in the cassette during operation of the flow pump 65.A pressure monitor or meter 87 arranged in the cassette may detect sucha high unexpected or undesirable pressure and results in an alarm and/orother action of the apparatus, such as shut-down of the operation. Thepressure monitor may be a piezo-electric pressure meter, which emits anelectric signal substantially proportional to the pressure inside thecassette.

The pressure meter 37, 87 may also be used for controlling the operationof the flow pump and/or the glucose pump. By closing the intermittentvalve 18 and the drain valve 17 and operating the flow pump 15 in theforward direction, a pressure should build up in the cassette 25, whichmay be controlled by the pressure meter 37, 87. The same control of theglucose pump may be performed. If pressure does not build up, a leak mayexist.

The pressure of the pressure meter 37, 87 may be measured or monitoredcontinuously. If a sudden and unexpected deviation of pressure ismeasured, an alarm is activated. This may happen if there is a kink onany of the tubes. If the valves do not operate properly, this may alsobe detected by the pressure monitor.

If there is a kink or occlusion at the patient line 82 during forwardoperation of the flow pump 65, a low-flow or no-flow will occur. Thisfact may remain undetected by the cassette pressure meter 87. However, aflow meter 90 arranged at the patient line 82 immediately before thepump segment may be used to detect a too small or absent flow. Inaddition, another flow meter 89 may be arranged between the intermittentvalve 68 and the patient connector 85.

The treatment is continued during a long time, at least six hours. In anembodiment, the treatment is performed daily during 16 hours. In anotherembodiment, the treatment is nocturnal and last for 8 hours. Before thetreatment, a new peritoneal fluid is introduced and after the treatment,all peritoneal fluid is drained. The difference between installed andremoved fluid may be measured in order to calculate obtainedultrafiltration.

It is known that peritoneal dialysis may result in large losses ofalbumin—a loss of up to 10 grains per day has been reported. Patientshaving overload of water, such as congestive heart failure patients, areextra sensitive to loss of albumin. This is because during waterexchange between blood and tissue, albumin plays a decisive role in sucha water balance. In addition, such patients often are malnourished andhave difficulties in replenishing the albumin in the blood. Thus, anyremoval of albumin should be counteracted.

FIG. 3 shows an albumin filter 92 arranged in the drain tube 81. Thefilter 92 will ensure that all substances equal to or larger thanalbumin will not pass to the drain bag 30. The final drain processstarts with opening of drain valve 67 and closing intermittent valve 68and operating pump 65 in the forward direction until all peritonealfluid has been pumped out of the peritoneal cavity. All albumin will beretained by the albumin filter 92. After the peritoneal cavity has beenemptied, the pump 65 may be operated in the reverse direction, in orderto return a small amount of fluid to the peritoneal cavity. Such a smallamount may be larger than the volume of tube 82 and cassette 75, such asabout 20 ml. Such reverse flow will return all albumin accumulatedinside the filter to the peritoneal cavity. The albumin is recovered bythe lymph system of the body.

The same principle may be used in any of the other embodiments.

The albumin filter may be arranged anywhere in the drain tube 81, forexample integrated in the connector 32 between the drain tube and thedrain bag. In this manner, the filter may be exchangeable.

Another important fact assists in saving albumin, namely that noadsorption filter or dialyzer is arranged in the flow path during thereplenishment cycles.

Adsorption filters may be used in conventional peritoneal dialysis foradsorption of waste products not cleared by the failing kidney, such asurea and creatinine. Such adsorption filters may adsorb albumin, whichwould risk to aggravate the symptoms for a congestive heart failurepatient. The present embodiments do not use any filters comprisingmaterial that may adsorb albumin during the treatment time. To thecontrary, the tube set is as small as possible and has no obstacles inthe flow path, except for the pump 15 and the pinch valve 18. Finally,during the drain phase, the fluid passes through an albumin filter,which retains the albumin, which is then returned to the peritonealcavity and may be absorbed by the body lymph system. Thus, albumin lossis minimized.

In addition, the flow path does not comprise a dialyzer having largesurfaces, at which albumin may attach and be removed.

In addition, the tube set has a very small inner volume, about 10 mlplus the volume of the cassette, which may be about 5 ml.

It may be advantageous to agitate the peritoneal fluid in the peritonealcavity. In the embodiment according to FIG. 2, such agitation may beperformed by operating the flow pump 65 in the reverse direction duringa predetermined time of for example 5 minutes followed by normal flowdirection by operating the flow pump 65 in the forward direction. Theoperation in the reverse direction may be performed at a higher speedthan normal or at varying speeds. In the first embodiment according toFIG. 1, an agitation may be obtained by operating the flow pump 15 withdifferent speeds during the inflow of peritoneal fluid, for example 30seconds of high speed followed by several minutes of normal speed.Operation with different speed may also or alternatively be used in thesecond embodiment.

The flow speeds during operation of the apparatus should normally besmall in order not to exert unnecessary pressure on the peritonealcavity and membrane. A flow speed of 15 ml/min to 40 ml/min isappropriate. The glucose pump may operate at speeds of 0.1 ml/min to 3ml/min. During drain, the flow pump 65 may be operated at a higher speedof up to about 170 ml/min.

The glucose bag may comprise glucose at a concentration of 10% to 20%(up to 40%) and may have a volume of about 0.25 to 0.5 liter. The volumeof peritoneal fluid entered into the peritoneal cavity may be about 1 to3 liter, for example 1.5 liter. The peritoneal fluid may comprise ionsof sodium 132 mM (mmole/liter), potassium 2 mM, calcium 2.5 mM,magnesium 0.5 mM, chloride 95 mM and lactate 40 mM. Lactate may bereplaced by acetate or bicarbonate. The initial glucose concentrationmay be about 1.5% or lower, as indicated above.

The fact that glucose is added from a glucose concentration bag isadvantageous, since glucose concentration can be sterilized withoutformation of toxic end products (AGE:s).

If sodium ions should be removed, the sodium ion concentration may belowered to 95 mM or lower. The potassium concentration may be lowered to1 mM or less (0 mM).

In the claims, the term “comprises/comprising” does not exclude thepresence of other elements or steps. Furthermore, although individuallylisted, a plurality of means, elements or method steps may beimplemented by e.g. a single unit. Additionally, although individualfeatures may be included in different claims or embodiments, these maypossibly advantageously be combined, and the inclusion in differentclaims does not imply that a combination of features is not feasibleand/or advantageous. In addition, singular references do not exclude aplurality. The terms “a”, “an”, “first”, “second” etc. do not preclude aplurality. Reference signs in the claims are provided merely as aclarifying example and shall not be construed as limiting the scope ofthe claims in any way.

Although the present invention has been described above with referenceto specific embodiment and experiments, it is not intended to be limitedto the specific form set forth herein. Rather, the invention is limitedonly by the accompanying claims and, other embodiments than thosespecified above are equally possible within the scope of these appendedclaims.

1. An apparatus for ultrafiltration of a patient, comprising: a patienttube configured to be connected to a patient line for access to aperitoneal fluid in a peritoneal cavity of the patient, a flow pump; anintermittent bag configured for receiving a portion of said peritonealfluid, said portion of said peritoneal fluid being removed from theperitoneal cavity using said patient tube by said flow pump and saidportion of said peritoneal fluid being returned to the peritoneal cavityusing said patient tube by said flow pump; a glucose tube for connectionof a glucose bag configured to provide concentrated glucose to saidportion of said peritoneal fluid before or during being returned to theperitoneal cavity, whereby the concentrated glucose is diluted in saidportion of said peritoneal fluid; whereby the apparatus is configured toreplenish glucose to said portion of said peritoneal fluid beingreturned to the peritoneal cavity to maintain a concentration of glucosesubstantially constant in the peritoneal cavity; wherein the apparatusis arranged without any adsorbent material.
 2. The apparatus accordingto claim 1, further comprising: a glucose pump arranged in said glucosetube and configured for pumping concentrated glucose to said portion ofsaid peritoneal fluid.
 3. The apparatus according to claim 1, furthercomprising: a mixing space having a first port connected to said glucosetube for adding concentrated glucose to said space; and a second portconnected to said intermittent bag and a third port connected to saidpatient tube for removing and returning said portion of said peritonealfluid between the intermittent bag and the mixing space and theperitoneal cavity.
 4. The apparatus according to claim 1, wherein theintermittent bag is smaller than 200 ml.
 5. The apparatus according toclaim 4, wherein the intermittent bag is 160 ml.
 6. The apparatusaccording to claim 1, wherein said mixing space comprises: a cassettehaving first, second, third and fourth ports; wherein said patient tubeis connected to said first port; said intermittent bag is connected tosaid second port via an intermittent tube; a drain tube is connected tosaid third port, said drain tube being arranged for connection to adrain bag, said glucose tube is connected to said fourth port.
 7. Anapparatus for ultrafiltration of a patient, comprising: a patient tubeconfigured to be connected to a patient line for access to a peritonealfluid in a peritoneal cavity of the patient, a flow pump; anintermittent bag configured for receiving a portion of said peritonealfluid, said portion of said peritoneal fluid being removed from theperitoneal cavity using said patient tube by said flow pump and saidportion of said peritoneal fluid being returned to the peritoneal cavityusing said patient tube by said flow pump; a glucose tube for connectionof a glucose bag configured to provide concentrated glucose to saidportion of said peritoneal fluid before or during being returned to theperitoneal cavity, whereby the concentrated glucose is diluted in saidportion of said peritoneal fluid; whereby the apparatus is configured toreplenish glucose to said portion of said peritoneal fluid beingreturned to the peritoneal cavity to maintain a concentration of glucosesubstantially constant in the peritoneal cavity; and wherein theapparatus is arranged without any dialyzer.
 8. The apparatus accordingto claim 7, further comprising: a glucose pump arranged in said glucosetube and configured for pumping concentrated glucose to said portion ofsaid peritoneal fluid.
 9. The apparatus according to claim 7, furthercomprising: a mixing space having a first port connected to said glucosetube for adding concentrated glucose to said mixing space; and a secondport connected to said intermittent bag and a third port connected tosaid patient tube for removing and returning said portion of saidperitoneal fluid between the intermittent bag and the mixing space andthe peritoneal cavity.
 10. The apparatus according to claim 7, whereinthe intermittent bag is smaller than 200 ml.
 11. The apparatus accordingto claim 10, wherein the intermittent bag is 160 ml.
 12. The apparatusaccording to claim 7, wherein said mixing space comprises: a cassettehaving first, second, third and fourth ports; wherein said patient tubeis connected to said first port; said intermittent bag is connected tosaid second port via an intermittent tube; a drain tube is connected tosaid third port, said drain tube being arranged for connection to adrain bag; said glucose tube is connected to said fourth port.
 13. Amethod for ultrafiltration of a patient, which patient has a peritonealfluid in a peritoneal cavity, comprising: removing a portion of saidperitoneal fluid from peritoneal cavity to an intermittent bag by a flowpump; subsequent to said removing, returning said portion of saidperitoneal fluid to said peritoneal cavity from said intermittent bag;before or during returning of said portion of said peritoneal fluid,adding concentrated glucose to said portion of said peritoneal fluid fordilution of said concentrated glucose in said portion of said peritonealfluid; repeating said removing and returning of said portion of saidperitoneal fluid and said adding of concentrated glucose intermittently,whereby the glucose is diluted and replenished intermittently; whereinthe removed portion of said peritoneal fluid and the returned portion ofsaid peritoneal fluid pass through a flow path, which is free fromadsorbent materials.
 14. The method according to claim 13, furthercomprising: repeating said removing and returning of said portion ofsaid peritoneal fluid and said adding of concentrated glucoseintermittently with a period of not greater than 60 minutes, whereby theglucose is diluted and replenished intermittently.
 15. The methodaccording to claim 13, further comprising: removal of said portion ofsaid peritoneal fluid during a removal period; returning of said portionof said peritoneal fluid with added concentrated glucose during areturning period stopping the flow pump during a stop period; wherebysaid removal period and said returning period and said stop period formsa replenishment period; repeating said removing step, returning step andstopping step; whereby said stop period is between 0 and 50 minutes. 16.A method for ultrafiltration of a patient, which patient has aperitoneal fluid in a peritoneal cavity, comprising: removing a portionof said peritoneal fluid from the peritoneal cavity to an intermittentbag by a flow pump; subsequent to said removing, returning said portionof said peritoneal fluid to said peritoneal cavity from saidintermittent bag; before or during returning of said portion of saidperitoneal fluid, adding concentrated glucose to said portion of saidperitoneal fluid for dilution of said concentrated glucose in saidportion of said peritoneal fluid; wherein the removed portion of saidperitoneal fluid and the returned portion of said peritoneal fluid passthrough flow paths, which are free from dialyzers.
 17. The methodaccording to claim 16, further comprising: repeating said removing andreturning of said portion of said peritoneal fluid and said adding ofconcentrated glucose intermittently with a period of not greater than 60minutes, whereby the glucose is diluted and replenished intermittently.18. The method according to claim 16, further comprising: removal ofsaid portion of said peritoneal fluid during a removal period; returningof said portion of said peritoneal fluid with added concentrated glucoseduring a returning period stopping the flow pump during a stop period;whereby said removal period and said returning period and said stopperiod forms a replenishment period; repeating said removing step,returning step and stopping step; whereby said stop period is between 0and 50 minutes.